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The neurobiology underlying these oxytocin effects: The hypothalamic pathway that differs by sex: N. Scott et al., “A Sexually Dimorphic Hypothalamic Circuit Controls Maternal Care and Oxytocin Secretion,” Nature 525 (2016): 519. For an example of oxytocin working in the insular cortex to modify social interactions, see M. Carter-Rogers et al., “Insular Cortex Mediates Approach and Avoidance Response to Social Affective Stimuli,” Nature Neuroscience 21 (2018): 404. Likewise for oxytocin working in the amygdala: Y. Liu et al., “Oxytocin Modulates Social Value Representations in the Amygdala,” Nature Neuroscience 22 (2019): 633; J. Wahis et al., “Astrocytes Mediate the Effect of Oxytocin in the Central Amygdala on Neuronal Activity and Affective States in Rodents,” Nature Neuroscience 24 (2021): 529.
Oxytocin and parenting, including paternal behavior: O. Bosch and I. Neumann, “Both Oxytocin and Vasopressin Are Mediators of Maternal Care and Aggression in Rodents: From Central Release to Sites of Action,” Hormones and Behavior 61 (2012): 293; Y. Kozorovitskiy et al., “Fatherhood Affects Dendritic Spines and Vasopressin V1a Receptors in the Primate Prefrontal Cortex,” Nature Neuroscience 9 (2006): 1094; Z. Wang, C. Ferris, and G. De Vries “Role of Septal Vasopressin Innervation in Paternal Behavior in Prairie Voles,” Proceedings of the National Academy of Sciences of the United States of America 91 (1994): 400.
Genetic and epigenetic differences mediating individual differences in oxytocin sensitivity: Marsh et al., “The Influence of Oxytocin Administration on Responses to Infants and Potential Moderation by OXTR Genotype,” Psychopharmacology (Berlin) 224 (2012): 469; M. J. Bakermans-Kranenburg and M. H. van Ijzendoorn, “Oxytocin Receptor (OXTR) and Serotonin Transporter (5-HTT) Genes Associated with Observed Parenting,” Social Cognitive and Affective Neuroscience 3 (2008): 128; E. Hammock and L. Young, “Microsatellite Instability Generates Diversity in Brain and Sociobehavioral Traits,” Science 308 (2005): 1630.
Annals of totally irresistible findings: M. Nagasawa et al., “Oxytocin-Gaze Positive Loop and the Coevolution of Human-Dog Bonds,” Science 348 (2015): 333. When a dog and its human gaze into each other’s eyes, both secrete oxytocin; administer oxytocin to one of the two and they gaze longer—eliciting more oxytocin secretion in the other. In other words, a hormonal system central to parental behavior and pair-bonding that is at least a hundred million years old has, in the last thirty thousand years, been co-opted for human/wolf interactions.
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Oxytocin effects on fear and anxiety: M. Yoshida et al., “Evidence That Oxytocin Exerts Anxiolytic Effects via Oxytocin Receptor Expressed in Serotonergic Neurons in Mice,” Journal of Neuroscience 29 (2009): 2259. Oxytocin working in the amygdala: D. Viviani et al., “Oxytocin Selectively Gates Fear Responses through Distinct Outputs from the Central Nucleus,” Science 333 (2011): 104; H. Knobloch et al., “Evoked Axonal Oxytocin Release in the Central Amygdala Attenuates Fear Response,” Neuron 73 (2012): 553; “Oxytocin Attenuates Amygdala Responses to Emotional Faces Regardless of Valence,” Biological Psychiatry 62 (2007): 1187; P. Kirsch et al., “Oxytocin Modulates Neural Circuitry for Social Cognition and Fear in Humans,” Journal of Neuroscience 25 (2005): 11489; I. Labuschagne et al., “Oxytocin Attenuates Amygdala Reactivity to Fear in Generalized Social Anxiety Disorder,” Neuropsychopharmacology 35 (2010): 2403.
Oxytocin blunting the stress-response: M. Heinrichs et al., “Social Support and Oxytocin Interact to Suppress Cortisol and Subjective Responses to Psychosocial Stress,” Biological Psychiatry 54 (2003): 1389.
Oxytocin effects on empathy, trust, and cooperation: S. Rodrigues et al., “Oxytocin Receptor Genetic Variation Relates to Empathy and Stress Reactivity in Humans,” Proceedings of the National Academy of Sciences of the United States of America 106 (2009): 21437; M. Kosfeld et al., “Oxytocin Increases Trust in Humans,” Nature 435 (2005): 673; A. Damasio, “Brain Trust,” Nature 435 (2005): 571; S. Israel et al., “The Oxytocin Receptor (OXTR) Contributes to Prosocial Fund Allocations in the Dictator Game and the Social Value Orientations Task,” Public Library of Science One 4 (2009): e5535; P. Zak, R. Kurzban, and W. Matzner, “Oxytocin Is Associated with Human Trustworthiness,” Hormones and Behavior 48 (2005): 522; T. Baumgartner et al., “Oxytocin Shapes the Neural Circuitry of Trust and Trust Adaptation in Humans,” Neuron 58 (2008): 639; J. Filling et al., “Effects of Intranasal Oxytocin and Vasopressin on Cooperative Behavior and Associated Brain Activity in Men,” Psychoneuroendocrinology 37 (2012): 447; A. Theodoridou et al., “Oxytocin and Social Perception: Oxytocin Increases Perceived Facial Trustworthiness and Attractiveness,” Hormones and Behavior 56 (2009): 128. A failure of replication: C. Apicella et al., “No Association between Oxytocin Receptor (OXTR) Gene Polymorphisms and Experimentally Elicited Social Preferences,” Public Library of Science One 5 (2010): e11153.
Oxytocin effects on aggression: M. Dhakar et al., “Heightened Aggressive Behavior in Mice with Lifelong versus Postweaning Knockout of the Oxytocin Receptor,” Hormones and Behavior 62 (2012): 86; J. Winslow et al., “Infant Vocalization, Adult Aggression, and Fear Behavior of an Oxytocin Null Mutant Mouse,” Hormones and Behavior 37 (2005): 145.
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C. De Dreu, “Oxytocin Modulates Cooperation within and Competition between Groups: An Integrative Review and Research Agenda,” Hormones and Behavior 61 (2012): 419; C. De Dreu et al., “The Neuropeptide Oxytocin Regulates Parochial Altruism in Intergroup Conflict among Humans,” Science 328 (2011): 1408; C. De Dreu et al., “Oxytocin Promotes Human Ethnocentrism,” Proceedings of the National Academy of Sciences of the United States of America 108 (2011): 1262.
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K. Parker et al., “Preliminary Evidence That Plasma Oxytocin Levels Are Elevated in Major Depression,” Psychiatry Research 178 (2010): 359; S. Freeman et al., “Effect of Age and Autism Spectrum Disorder on Oxytocin Receptor Density in the Human Basal Forebrain and Midbrain,” Translational Psychiatry 8 (2018): 257.
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R. Sapolsky, “Stress and the Brain: Individual Variability and the Inverted-U,” Nature Neuroscience 25 (2015): 1344.
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Effects of stress and stress hormones on the amygdala: J. Rosenkranz, E. Venheim, and M. Padival, “Chronic Stress Causes Amygdala Hyperexcitability in Rodents,” Biological Psychiatry 67 (2010): 1128; S. Duvarci and D. Pare, “Glucocorticoids Enhance the Excitability of Principal Basolateral Amygdala Neurons,” Journal of Neuroscience 27 (2007) 4482; A. Kavushansky and G. Richter-Levin, “Effects of Stress and Corticosterone on Activity and Plasticity in the Amygdala,” Journal of Neuroscience Research 84 (2006): 1580; P. Rodríguez Manzanares et al., “Previous Stress Facilitates Fear Memory, Attenuates GABAergic Inhibition, and Increases Synaptic Plasticity in the Rat Basolateral Amygdala,” Journal of Neuroscience 25 (2005): 8725.
Effects of stress and stress hormones on interactions between the amygdala and hippocampus: A. Kavushansky et al., “Activity and Plasticity in the CA1, the Dentate Gyrus, and the Amygdala Following Controllable Versus Uncontrollable Water Stress,” Hippocampus 16 (2006): 35; H. Lakshminarasimhan and S. Chattarji, “Stress Leads to Contrasting Effects on the Levels of Brain Derived Neurotrophic Factor in the Hippocampus and Amygdala,” Public Library of Science One 7 (2012): e30481; S. Ghosh, T. Laxmi, and S. Chattarji, “Functional Connectivity from the Amygdala to the Hippocampus Grows Stronger after Stress,” Journal of Neuroscience 33 (2013): 7234.
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Behavioral effects of stress and stress hormones: S. Preston et al., “Effects of Anticipatory Stress on Decision-Making in a Gambling Task,” Behavioral Neuroscience 121 (2007): 257; P. Putman et al., “Exogenous Cortisol Acutely Influences Motivated Decision Making in Healthy Young Men,” Psychopharmacology 208 (2010): 257; P. Putman, E. Hermans, and J. van Honk, “Cortisol Administration Acutely Reduces Threat-Selective Spatial Attention in Healthy Young Men,” Physiology and Behavior 99 (2010): 294; K. Starcke et al., “Anticipatory Stress Influences Decision Making under Explicit Risk Conditions,” Behavioral Neuroscience 122 (2008): 1352.
Sex differences and stress/stress hormone effects: R. van den Bos, M. Harteveld, and H. Stoop, “Stress and Decision-Making in Humans: Performance Is Related to Cortisol Reactivity, Albeit Differently in Men and Women,” Psychoneuroendocrinology 34 (2009): 1449; N. Lighthall, M. Mather, and M. Gorlick, “Acute Stress Increases Sex Differences in Risk Seeking in the Balloon Analogue Risk Task,” Public Library of Science One 4 (2009): e6002; N. Lighthall et al., “Gender Differences in Reward-Related Decision Processing under Stress,” Social Cognitive and Affective Neuroscience 7 (2012): 476.
Stress and stress hormone effects on aggression: D. Hayden-Hixson and C. Ferris, “Steroid-Specific Regulation of Agonistic Responding in the Anterior Hypothalamus of Male Hamsters,” Physiology and Behavior 50 (1991): 793; A. Poole and P. Brain, “Effects of Adrenalectomy and Treatments with ACTH and Glucocorticoids on Isolation-Induced Aggressive Behavior in Male Albino Mice,” Progress in Brain Research 41 (1974): 465; E. Mikics, B. Barsy, and J. Haller, “The Effect of Glucocorticoids on Aggressiveness in Established Colonies of Rats,” Psychoneuroendocrinology 32 (2007): 160; R. Böhnke et al., “Exogenous Cortisol Enhances Aggressive Behavior in Females, but Not in Males,” Psychoneuroendocrinology 35 (2010): 1034; K. Bertsch et al., “Exogenous Cortisol Facilitates Responses to Social Threat under High Provocation,” Hormones and Behavior 59 (2011): 428.
Stress and stress hormone effects on moral decision-making: K. Starcke, C. Polzer, and O. Wolf, “Does Everyday Stress Alter Moral Decision-Making?,” Psychoneuroendocrinology 36 (2011): 210; F. Youssef, K. Dookeeram, and V. Basdeo, “Stress Alters Personal Moral Decision Making,” Psychoneuroendocrinology 37 (2012): 491.
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For more details about this general topic, see chapter 4 in Sapolsky, Behave.
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Footnote: For a great history of the (re)discovery of adult neurogenesis, see M. Specter, “How the Songs of Canaries Upset a Fundamental Principle of Science,” New Yorker, July 23, 2001.
The behavioral consequences of adult neurogenesis: G. Kempermann, “What Is Adult Hippocampal Neurogenesis Good For?,” Frontiers of Neuroscience 16 (2022), doi.org/10.3389/fnins.2022.852680; Y. Li, Y. Luo, and Z. Chen, “Hypothalamic Modulation of Adult Hippocampal Neurogenesis in Mice Confers Activity-Dependent Regulation of Memory and Anxiety-Like Behavior,” Nature Neuroscience 25 (2022): 630; D. Seib et al., “Hippocampal Neurogenesis Promotes Preference for Future Rewards,” Molecular Psychiatry 26 (2021): 6317; C. Anacker et al., “Hippocampal Neurogenesis Confers Stress Resilience by Inhibiting the Ventral Dentate Gyrus,” Nature 559 (2018): 98.
Amid all this fascination, experience is also changing the consequential birth of those less flashy glial cells in the adult brain: A. Delgado et al., “Release of Stem Cells from Quiescence Reveals Gliogenic Domains in the Adult Mouse Brain,” Science 372 (2021): 1205.
The debate as to how much adult neurogenesis actually occurs in humans: S. Sorrells et al., “Human Hippocampal Neurogenesis Drops Sharply in Children to Undetectable Levels in Adults,” Nature 555 (2018): 377. For a retort: M. Baldrini et al., “Human Hippocampal Neurogenesis Persists throughout Aging,” Cell Stem Cell 22 (2018): 589. For an opinion piece with a similar viewpoint: G. Kempermann, F. Gage, and L. Aigner, “Human Neurogenesis: Evidence and Remaining Questions,” Cell Stem Cell 23 (2018): 25. Then a vote for the revolutionaries: S. Ranade, “Single-Nucleus Sequencing Finds No Adult Hippocampal Neurogenesis in Humans,” Nature Neuroscience 25 (2022): 2.
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R. Hamilton et al., “Alexia for Braille Following Filateral Occipital Stroke in an Early Blind Woman,” Neuroreport 11 (2000): 237; E. Striem-Amit et al., “Reading with Sounds: Sensory Substitution Selectively Activates the Visual Word Form Area in the Blind,” Neuron 76 (2012): 640; A. Pascual-Leone, “Reorganization of Cortical Motor Outputs in the Acquisition of New Motor Skills,” in Recent Advances in Clinical Neurophysiology, ed. J. Kinura and H. Shibasaki (Elsevier Science, 1996), pp. 304–8.
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S. Rodrigues, J. LeDoux, and R. Sapolsky, “The Influence of Stress Hormones on Fear Circuitry,” Annual Review of Neuroscience 32 (2009): 289.
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For a general review, see: B. Leuner and E. Gould, “Structural Plasticity and Hippocampal Function,” Annual Review of Psychology 61 (2010): 111.
Effects of stress on hippocampal structure: A. Magarinos and B. McEwen, “Stress-Induced Atrophy of Apical Dendrites of Hippocampal CA3c Neurons: Involvement of Glucocorticoid Secretion and Excitatory Amino Acid Receptors,” Neuroscience 69 (1995): 89; A. Magarinos et al., “Chronic Psychosocial Stress Causes Apical Dendritic Atrophy of Hippocampal CA3 Pyramidal Neurons in Subordinate Tree Shrews,” Journal of Neuroscience 16 (1996): 3534; B. Eadie, V. Redila, and B. Christie, “Voluntary Exercise Alters the Cytoarchitecture of the Adult Dentate Gyrus by Increasing Cellular Proliferation, Dendritic Complexity, and Spine Density,” Journal of Comparative Neurology 486 (2005): 39; A. Vyas et al., “Chronic Stress Induces Contrasting Patterns of Dendritic Remodeling in Hippocampal and Amygdaloid Neurons,” Journal of Neuroscience 22 (2002): 6810.
Neuroplasticity related to depression: P. Videbach and B. Revnkilde, “Hippocampal Volume and Depression: A Meta-analysis of MRI Studies,” American Journal of Psychiatry 161 (2004): 1957; L. Gerritsen et al., “Childhood Maltreatment Modifies the Relationship of Depression with Hippocampal Volume,” Psychological Medicine 45 (2015): 3517.
Effects of exercise and stimulation on neuroplasticity: J. Firth et al., “Effect of Aerobic Exercise on Hippocampal Volume in Humans: A Systematic Review and Meta-analysis,” Neuroimage 166 (2018): 230; G. Clemenson, W. Deng, and F. Gage, “Environmental Enrichment and Neurogenesis: From Mice to Humans,” Current Opinion in Behavioral Sciences 4 (2015): 56.
Estrogen and neuroplasticity: B. McEwen, “Estrogen Actions throughout the Brain,” Recent Progress in Hormone Research 57 (2002): 357; N. Lisofsky et al., “Hippocampal Volume and Functional Connectivity Changes during the Female Menstrual Cycle,” Neuroimage 118 (2015): 154; K. Albert et al., “Estrogen Enhances Hippocampal Gray-Matter Volume in Young and Older Postmenopausal Women: A Prospective Dose-Response Study,” Neurobiology of Aging 56 (2017): 1.
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N. Brebe et al., “Pair-Bonding, Fatherhood, and the Role of Testosterone: A Meta-analytic Review,” Neuroscience & Biobehavioral Reviews 98 (2019): 221; Y. Ulrich-Lai et al., “Chronic Stress Induces Adrenal Hyperplasia and Hypertrophy in a Subregion-Specific Manner,” American Journal of Physiology: Endocrinology and Metabolism 291 (2006): E965.
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J. Foster, “Modulating Brain Function with Microbiota,” Science 376 (2022): 936; J. Cryan and S. Mazmanian, “Microbiota-Brain Axis: Context and Causality,” Science 376 (2022): 938. Also: C. Chu et al., “The Microbiota Regulate Neuronal Function and Fear Extinction Learning,” Nature 574 (2019): 543. A great example of events over the course of weeks to months changing behavior without conscious awareness can be found in S. Mousa, “Building Social Cohesion between Christians and Muslims through Soccer in Post-ISIS Iraq,” Science 369 (2020): 866. Soccer teams in a league were experimentally composed of either solely Christian players or a mixture of the two religions (without players being aware of this intentional design as part of a study). Spending a season playing with Muslim teammates made Christian players far more affiliative with their Muslim teammates on the field—without changing overtly stated attitudes about Muslims.
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For more details about this general topic, see chapter 5 in Sapolsky, Behave.
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A. Caballero, R. Granbeerg, and K. Tseng, “Mechanisms Contributing to Prefrontal Cortex Maturation during Adolescence,” Neuroscience & Biobehavioral Reviews 70 (2016): 4; K. Delevich et al., “Coming of Age in the Frontal Cortex: The Role of Puberty in Cortical Maturation,” Seminars in Cell & Developmental Biology 118 (2021): 64. Chronically disrupting sleep in adolescent mice changes the workings of the dopamine reward system in adulthood, and not in a good direction; in other words, our mothers were right when urging us to resist the teenage pull toward crazy sleeping hours: W. Bian et al., “Adolescent Sleep Shapes Social Novelty Preference in Mice,” Nature Neuroscience 25 (2022): 912.
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E. Sowell et al., “Mapping Continued Brain Growth and Gray Matter Density Reduction in Dorsal Frontal Cortex: Inverse Relationships during Postadolescent Brain Maturation,” Journal of Neuroscience 21 (2021): 8819; J. Giedd, “The Teen Brain: Insights from Neuroimaging,” Journal of Adolescent Health 42 (2008): 335.
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Footnote: C. González-Acosta et al., “von Economo Neurons in the Human Medial Frontopolar Cortex,” Frontiers in Neuroanatomy 12 (2018), doi.org/10.3389/fnana.2018.00064; R. Hodge, J. Miller, and E. Lein, “Transcriptomic Evidence That von Economo Neurons Are Regionally Specialized Extratelencephalic-Projecting Excitatory Neurons,” Nature Communications 11 (2020): 1172.
